[This corrects the article DOI: 10.36469/jheor.2024.124604.].

Type 2 diabetes and obesity rates continue to rise. Type 2 diabetes affects 1-2 million new individuals annually. Despite a wide range of treatment options for type 2 diabetes, many people still fail to achieve therapeutic goals. Treating type 2 diabetes more proactively with a pathophysiologic approach can ensure higher rates of success and reduce complications. This article summarizes the progressive understanding of the pathophysiology of diabetes, draws a connection between illness and beta-cell health, and introduces the pathophysiologic approach to type 2 diabetes and its focus on beta-cell preservation. This article compiled clinical data, evidence-based medicine, and experimental results to create a comprehensive narrative review.

Neonatal porcine islets (NPIs) can mature into a mixed population of endocrine cells that can restore glucose control in mice, pigs, and non-human primates, representing a potential alternative islet source for clinical beta cell replacement therapy. However, it remains unclear how conditions in the recipient influence the maturation and function of these cells. Here, we investigated the impact of host sex on NPIs implanted under the kidney capsule of male and female B6.129S7-Rag1tm1Mom (B6/Rag-/-) mice.

Diabetic mice were transplanted with 3000 NPIs under the kidney capsule. All mice were monitored for reversal of hyperglycemia and glucose clearance at 8- and 20-weeks post-transplant. Grafts were assessed for cell composition and insulin content.

Female mice demonstrated improved glucose clearance at 8- and 20-weeks post-transplant compared to their male counterparts. Improved glucose clearance correlated with accelerated diabetes reversal in females (8 weeks vs. 12 weeks in males) and increased rates of euglycemic achievement (17/18 in females vs. 14/19 in males). However, grafts collected from male mice exhibited an increased percentage of insulin-positive cells as well as increased insulin content.

The sex of the host influences the outcomes of NPI transplantation, showcasing the relevance of understanding the role of sex as a biological variable in islet transplantation.

Background Strengthening the role of diabetes nurse specialists, by expanding their knowledge and clinical expertise, can significantly contribute to managing diabetes mellitus and its complications. Objectives To assess and compare the impact of nurse-led diabetic follow-up clinics compared to conventional care on glycated hemoglobin (HbA1c) levels and diabetes treatment satisfaction among adult patients with type 2 diabetes mellitus (T2DM) seeking treatment in tertiary care settings. Material and methods A prospective, single-center, parallel-group randomized trial was conducted in a routine Diabetic Outpatient Department (OPD) at a tertiary care setting. After accounting for the loss to follow-up, 106 participants completed the trial. Diagnosed cases of T2DM with more than two records of HbA1c outside of the recommended range (>7%) and receiving insulin therapy for treatment were the inclusion criteria. The intervention included insulin titration and regular follow-up with the trained diabetes nurse for diabetes care and management. Endpoint measurements of HbA1c levels and diabetes treatment satisfaction were taken after three to six months of treatment to analyze the impact of the intervention. Results Participants receiving care through a nurse-led diabetic follow-up clinic had a decrease in HbA1c levels after the intervention, with an average paired difference of 1.75 (1.12 to 2.38), statistically significant at the 0.05 level of significance. Although HbA1c levels in the Control Group also decreased after the standard intervention, with a mean paired difference of 0.64 (0.03 to 1.25), it did not reach statistical significance, with a p-value of 0.05 at the 0.05 level of significance. However, patients' HbA1c levels between the Intervention and Control Groups at baseline (p = 0.101) and post-intervention (p = 0.369) were not statistically significant at the 0.05 level of significance. Furthermore, participants in the Intervention Group achieved better glycemic control, as measured by self-reported satisfaction with regards to hyperglycemia (-0.95 ± 1.43 vs. 0.39 ± 1.88, p = 0.001) and hypoglycemia (-0.35 ± 1.02 vs. 0.71 ± 1.1, p < 0.001) levels. Conclusion The nurse-led diabetes follow-up clinic was found to be an invaluable service, and the addition of a diabetes specialist nurse as part of the treatment team can alter the conventional pathway for diabetes treatment.

B-thalassemia is a genetic disorder that leads to reduced or absent β-globin chains, often resulting in endocrine abnormalities due to iron overload, chronic anemia, and hypoxia. This study investigates the prevalence and risk factors for glucose metabolism disturbances in transfusion-dependent β-thalassemia (TDT) patients, focusing on pancreatic iron overload and its association with other iron biomarkers.

We studied two groups of TDT patients (2018-2022) at Hippokration General Hospital: Group 1 (no glucose metabolism impairment, n = 46) and Group 2 (with impaired glucose tolerance or diabetes mellitus, n = 18). Patients were assessed for factors contributing to glucose disturbances, and laboratory data were analyzed. Type 2 diabetes was diagnosed per American Diabetes Association criteria, and impaired glucose tolerance was defined by OGTT results. A multivariate logistic regression identified potential independent risk factors. In a subset of patients on iron chelation therapy, we examined the relationship between pancreatic, liver, and heart iron overload (T2* MRI) and glucose/ferritin levels.

Age and elevated serum GGT levels were significantly associated with impaired glucose metabolism (p = 0.02). Beta-blocker use was correlated with glucose disturbances (p = 0.02), but multivariate analysis revealed no significant independent risk factors. A significant relationship was found between pancreatic and heart iron overload (r = 0.45, p = 0.04).

Elevated GGT levels suggest that oxidative stress and liver dysfunction play a key role in glucose metabolism disturbances. Pancreatic MRI T2* may help predict heart iron overload. Further research is needed to identify reliable biomarkers for glucose regulation in TDT.

Diabetes mellitus (DM) is a multifaceted disorder with a pandemic spread and a remarkable burden of cardiovascular mortality and morbidity. Diabetic cardiomyopathy (DBCM) has been increasingly recognized as the development of cardiac dysfunction, which is accompanied by heart failure (HF) symptoms in the absence of obvious reasons like ischemic heart disease, hypertension, or valvulopathies. Several pathophysiological mechanisms have been proposed, including metabolic disorders (e.g., glycation products), oxidative stress, low-grade inflammation, mitochondrial dysfunction, etc., which should guide the development of new therapeutic strategies. Up to now, HF treatment has not differed between patients with and without diabetes, which limits the expected benefits despite the high cardiovascular risk in the former group. However, DBCM patients may require different management, which prioritize anti-diabetic medications or testing other novel therapies. This review aims to appraise the challenges and prospectives of the individualized pharmaceutical therapy for DBCM.

Enterobacter asburiae (E. asburiae) is a gram-negative rod-shaped bacterium which has emerging significance as an opportunistic pathogen having high virulence pattern and drug resistant properties. In this study, we present the detailed analysis of the whole genome sequence of a multidrug-resistant (MDR) E. asburiae strain BDW1M3 from Bangladesh. The isolate was collected from an infected foot wound of a diabetic foot ulcer patient. Through sophisticated genomic techniques encompassing whole genome sequencing and in-depth bioinformatic analyses, this research unveils a profound understanding of the isolate's antimicrobial resistance patterns, virulence determinants, biosynthetic gene clusters, metabolic pathways and pathogenic potential. The isolate displayed resistance to Ampicillin, Fosfomycin, Cefoxitin, Tigecycline, Meropenem, Linezolid, Vancomycin antibiotics and demonstrated the capacity for biofilm formation. Several antimicrobial resistance genes such as blaACT-2,fosA2, baeR, qnrE2, vanA and numbers of virulence genes including ybaJ, csrA, barA, uvrY, pgaD, hlyD, hlyC, terC, purD were detected. Metal resistance genes investigation revealed the presence of cusCFBA operon system, and many other genes including zntA, zitB, czrB. Prophage region of Myoviridae was detected. Comparative genomics with 47 whole genome sequence (n = 47) shed light on the genetic diversity of E. asburiae strains from diverse sources and countries, with a notable observation that strains from both human and non-human origins exhibited significant pathogenicity potential, genomic and phylogenomic relations hinting at potential cross-species transmission. Pangenome analysis indicated toward an expanding pangenome of E. asburiae. Further research and in-depth comprehensive studies are required to investigate the prevalence of E. asburiae in Bangladesh and emphasize towards unraveling the bacterium's inherent pathogenic potential and the intricate molecular mechanisms that underlie its resistance traits and virulence properties.

India is referred to as the "Diabetes Capital of the World" with a weighted prevalence of diabetes of 11.4%. In addition to microvascular and macrovascular complications, musculoskeletal manifestations of diabetes mellitus (MMDMs) also cause significant pain, morbidity, and a decrease in quality of life. Previous studies in our country were from tertiary healthcare centres, and the actual community-based prevalence of MMDMs is unknown. The study aims to determine the prevalence of MMDMs and the factors associated with them in the Ernakulam district of Kerala.

A community-based cross-sectional study was done in 600 adults with diabetes in the Ernakulam district of Kerala. Cluster sampling was adopted. Through the probability proportional to sample size method, 20 clusters were identified with each having 30 participants. The study participants were clinically examined for various MMDMs.

The prevalence of MMDMs was found to be 44.83%. Osteoarthritis knee emerged as the most prevalent MMDM involving 22% of the participants, followed by frozen shoulder, in 12.2%. Diabetic cheiroarthropathy, trigger finger, and carpal tunnel syndrome were noted in 6.7%, 4.7%, and 3.8% of participants, respectively. Multivariable analysis showed a significant association between MMDMs and increased BMI, higher socioeconomic status, longer duration of diabetes, and unsatisfactory physical activity.

This study highlights the need for regular musculoskeletal system assessment in patients with diabetes which needs to be made mandatory in clinical practice and also conducting screening for the same in the community level to prevent further complications and to improve quality of life.

Complex network is an effective approach to studying complex diseases, and provides another perspective for understanding their pathological mechanisms by illustrating the interactions between various factors of diseases. Type 2 diabetes mellitus (T2DM) is a complex polygenic metabolic disease involving genetic and environmental factors. By combining the complex network approach with biological data, this study constructs a pathway-based weighted network model of T2DM-related genes to explore the interrelationships between genes, here a weight is assigned to each edge in terms of the number of the same pathways in which the two nodes (genes) connected to the edge are involved. The edge weights can reflect differences in the strength of connections (interactions) between nodes (genes), which intuitively reflect the extent of biological correlations between genes and contribute to the importance of the nodes. Analysis of statistical and topological characteristics shows that the edge weights are correlated to the network topology, and the edge weight distribution decays as a power-law. The disparity of the weights indicates that the edge weight distribution for the nodes with the same degree is of approximately equal weights; and most edges with the higher weights tend to connect with the higher degree nodes. To determine the key hub genes of the weighted network, an integrated ranking index is used to comprehensively reflect the contribution of the three indices (strength, degree and number of pathways) of nodes; by taking the threshold of integrated ranking index greater than 0.56, 12 key hub genes are identified: MAPK1, PIK3CD, PIK3CA, PIK3R1, AKT2, AKT1, KRAS, TNF, MAPK8, PRKCA, IL6 and MTOR. These genes should play an important role in the occurrence and development of T2DM, and can be regarded as potential therapeutic targets for further biological and medical research on their functions in T2DM. It can be expected that combining complex network approach with other data analysis techniques can provide more clues for exploring the pathogenesis and treatment of T2DM and other complex diseases in the future.

Background: Two million Americans have type 1 diabetes (T1DM). Innovative treatments have standardized insulin delivery and improved outcomes for patients, but patients' access to such technologies depends on social determinants of health, including insurance coverage, proper diagnosis, and appropriate patient supports. Prior estimates of US prevalence, incidence, and patient characteristics have relied on data from select regions and younger ages and miss important determinants. Objectives: This study sought to use large, nationally representative healthcare claims data sets to holistically estimate the size of the current US population with T1DM and investigate geographic nuances in prevalence and incidence, patient demographics, insurance coverage, and device use. This work also aimed to project T1DM population growth over the next 10 years. Methods: We used administrative claims from 4 sources to identify prevalent and incident T1DM patients in the US, as well as various demographic and insurance characteristics of the patient population. We combined this data with information from national population growth projections and literature to construct an actuarial model to project growth of the T1DM population based on current trends and scenarios for 2024, 2029, and 2033. Results: We estimated 2.07 million T1DM patients nationally across all insurance coverages in our 2024 baseline model year: 1.79 million adults (≥20 years) and 0.28 million children. This represents a US T1DM prevalence rate of 617 per 100 000 and an incidence rate of 0.016%. By 2033, we project the US population with T1DM will grow by about 10%, reaching approximately 2.29 million patients. Discussion: Our results showed important differences in T1DM prevalence and incidence across regions, payers, and ethnic groups. This suggests studies based on more geographically concentrated data may miss important variation in prevalence and incidence across regions. It also indicates T1DM prevalence tends to vary by income, consistent with several international studies. Conclusions: Accurate projections of T1DM population growth are critical to ensure appropriate healthcare coverage and reimbursement for treatments. Our work supports future policy and research efforts with 2024, 2029, and 2033 projections of demographics and insurance coverage for people with T1DM.

Six Schiff bases with general name 5-(diethylamino)-2-(((halophenyl)imino)methyl)phenol (where halo = 4-fluoro (H1), 2-fluoro (H2), 2-bromo (H3), 4-bromo (H4), 4-chloro (H5) and 3-chloro-4-fluoro (H6)) were prepared by the condensation reaction between 4-(diethylamino)salicylaldehyde and suitable halogenated aromatic amines. The six halogenated Schiff bases were elucidated using different spectroscopic techniques and the structure of H3 and H6 were confirmed using single-crystal X-ray crystallography. The bond lengths of C7-N1, C7-C8 and C8-C9 obtained from structural analysis for both compounds depicted their enol-tautomeric characteristic form. The Hirshfeld analysis revealed that H‧‧‧H intermolecular contacts contributed most towards the Hirshfeld surfaces of both H3 (47.6%) and H6 (39.9%). Quantum chemical calculation studies showed that H1 and H2 have the highest and lowest energy band gap (∆E = 3.80 eV for H1 and ∆E = 3.73 eV for H2), depicting H2 and H1 as the most and least chemically reactive respectively among all the compounds. α-Amylase and α-glucosidase assay were used to evaluate the antidiabetes prowess of the synthesized compounds. All the compounds exhibited lower IC50 values than acarbose (reference drug) in α-amylase assay experiments and H5 with lowest IC50 value of 63.54 μM could be suggested to have the highest α-amylase inhibitory potential among the test samples. For α-glucosidase assay, H1-H6 displayed good antidiabetic potential. However, none of the compounds outshined acarbose with H6 having highest α-glucosidase inhibitory potential when compared to others i.e., IC50 of H6 = 60.89 μM and IC50 of acarbose = 51.42 μM. We measured the antioxidant potential of H1-H6 exploring 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric reducing ability power (FRAP) assays. The DPPH as well as NO radical scavenging assay showed that all the compounds exhibited excellent antioxidant results with some of the compounds surpassing catechin (reference drug). Compound H5 with IC50 values of 30.32 mM and 31.73 mM outshined catechin with IC50 values of 31.17 mM and 140.62 mM for DPPH and NO assays respectively. All the compounds fell within the threshold of Lipinski's Ro5 projecting them as orally bioavailable and less toxic future therapeutics.

The discovery of insulin by Frederick G Banting and his colleagues in 1921 marked a pivotal moment in medical history. Born in Ontario, Canada, in 1891, Banting's childhood was impacted by the death of his closest friend, Jane, who died of diabetes mellitus at a young age. This personal tragedy profoundly influenced him to choose a career in medicine and fueled his determination to find a cure for diabetes. This journey led to the discovery of Insulin with the help of Charles H Best and John JR Macleod, resulting in a Nobel Prize for this work. Their discoveries set the stage for advancements in clinical medicine and biotechnology, including developing recombinant insulin over 50 years later.

Owing to its promiscuous roles, poly (ADP-ribose) polymerase-1 (PARP-1) is involved in various neurological disorders including several retinal pathologies. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus affecting the retina. In the present review, we highlight the importance of PARP-1 participation in pathophysiology of DR and discuss promising potential inhibitors for treatment. A high glucose level enhances PARP-1 expression; PARP inhibitors have gained attention due to their potential therapeutic effects in DR. They target different checkpoints (blocking nuclear transcription factor (NF-κB) activation; oxidative stress protection, influence on vascular endothelial growth factor (VEGF) expression, impacting neovascularization). Nowadays, there are several improved clinical PARP-1 inhibitors with different allosteric effects. Combining PARP-1 inhibitors with other compounds is another promising option in DR treatments. Besides pharmacological inhibition, genetic disruption of the PARP-1 gene is another approach in PARP-1-initiated therapies. In terms of future treatments, the limitations of single-target approaches shift the focus onto combined therapies. We emphasize the importance of multi-targeted therapies, which could be effective not only in DR, but also in other ischemic conditions.

The incidence of diabetes, including type 2 diabetes (T2DM), is increasing sharply worldwide. To reverse this, more effective approaches in prevention and treatment are needed. In our review, we sought to summarize normal insulin action and the pathways that primarily influence the development of T2DM. Normal insulin action involves mitogenic and metabolic pathways, as both are important in normal metabolic processes, regeneration, etc. However, through excess energy, both can be hyperactive or attenuated/inactive leading to disturbances in the cellular and systemic regulation with the consequence of cellular stress and systemic inflammation. In this review, we detailed the beneficial molecular changes caused by some important components of nutrition and by exercise, which act in the same molecular targets as the developed drugs, and can revert the damaged pathways. Moreover, these induce entire networks of regulatory mechanisms and proteins to restore unbalanced homeostasis, proving their effectiveness as preventive and complementary therapies. These are the main steps for success in prevention and treatment of developed diseases to rid the body of excess energy, both from stored fats and from overnutrition, while facilitating fat burning with adequate, regular exercise in healthy people, and together with necessary drug treatment as required in patients with insulin resistance and T2DM.

Diabetes, a complex multisystem metabolic disorder characterized by hyperglycemia, leads to complications that reduce quality of life and increase mortality. Diabetes pathophysiology includes dysfunction of beta cells, adipose tissue, skeletal muscle, and liver. Type 1 diabetes (T1D) results from immune-mediated beta cell destruction. The more prevalent type 2 diabetes (T2D) is a heterogeneous disorder characterized by varying degrees of beta cell dysfunction in concert with insulin resistance. The strong association between obesity and T2D involves pathways regulated by the central nervous system governing food intake and energy expenditure, integrating inputs from peripheral organs and the environment. The risk of developing diabetes or its complications represents interactions between genetic susceptibility and environmental factors, including the availability of nutritious food and other social determinants of health. This perspective reviews recent advances in understanding the pathophysiology and treatment of diabetes and its complications, which could alter the course of this prevalent disorder.

Hormones play a crucial role in maintaining the normal human physiology. By acting as chemical messengers that facilitate the communication between different organs, tissues and cells of the body hormones assist in responding appropriately to external and internal stimuli that trigger growth, development and metabolic activities of the body. Any abnormalities in the hormonal composition and balance can lead to devastating health consequences. Hormones have been important therapeutic agents since the early 20th century, when it was realized that their exogenous supply could serve as a functional substitution for those hormones which are not produced enough or are completely lacking, endogenously. Insulin, the pivotal anabolic hormone in the body, was used for the treatment of diabetes mellitus, a metabolic disorder due to the absence or intolerance towards insulin, since 1921 and is the trailblazer in hormone therapeutics. At present the largest market share for therapeutic hormones is held by insulin. Many other hormones were introduced into clinical practice following the success with insulin. However, for the six decades following the introduction the first therapeutic hormone, there was no reliable method for producing human hormones. The most common source for hormones were animals, although semisynthetic and synthetic hormones were also developed. However, none of these were optimal because of their allergenicity, immunogenicity, lack of consistency in purity and most importantly, scalability. The advent of recombinant DNA technology was a game changer for hormone therapeutics. This revolutionary molecular biology tool made it possible to synthesize human hormones in microbial cell factories. The approach allowed for the synthesis of highly pure hormones which were structurally and biochemically identical to the human hormones. Further, the fermentation techniques utilized to produce recombinant hormones were highly scalable. Moreover, by employing tools such as site directed mutagenesis along with recombinant DNA technology, it became possible to amend the molecular structure of the hormones to achieve better efficacy and mimic the exact physiology of the endogenous hormone. The first recombinant hormone to be deployed in clinical practice was insulin. It was called biosynthetic human insulin to reflect the biological route of production. Subsequently, the biochemistry of recombinant insulin was modified using the possibilities of recombinant DNA technology and genetic engineering to produce analogues that better mimic physiological insulin. These analogues were tailored to exhibit pharmacokinetic and pharmacodynamic properties of the prandial and basal human insulins to achieve better glycemic control. The present chapter explores the principles of genetic engineering applied to therapeutic hormones by reviewing the evolution of therapeutic insulin and its analogues. It also focuses on how recombinant analogues account for the better management of diabetes mellitus.

Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium-glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM.

Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of obesity in both developing and underdeveloped countries has been reached. According to the World Obesity Atlas 2023 report, 38% of the world population are presently either obese or overweight. One of the causes of obesity is an imbalance of energy intake and energy expenditure, where nutritional imbalance due to consumption of high-calorie fast foods play a pivotal role. The dynamic interactions among different risk factors of obesity are highly complex; however, the underpinnings of hyperglycemia and dyslipidemia for obesity incidence are recognized. Fast foods, primarily composed of soluble carbohydrates, non-nutritive artificial sweeteners, saturated fats, and complexes of macronutrients (protein-carbohydrate, starch-lipid, starch-lipid-protein) provide high metabolic calories. Several experimental studies have pointed out that dairy proteins and peptides may modulate the activities of risk factors of obesity. To justify the results precisely, peptides from dairy milk proteins were synthesized under in vitro conditions and their contributions to biomarkers of obesity were assessed. Comprehensive information about the impact of proteins and peptides from dairy milks on fast food-induced obesity is presented in this narrative review article.

The exponential increase in diabetes mellitus (DM) poses serious public health concerns. In this review, we focus on the role of leptin in type 2 DM. The peripheral actions of leptin consist of upregulating proinflammatory cytokines which play an important role in the pathogenesis of type 2 DM and insulin resistance. Moreover, leptin is known to inhibit insulin secretion and plays a significant role in insulin resistance in obesity and type 2 DM. A literature search was conducted on Medline, Cochrane, Embase, and Google Scholar for relevant articles published until December 2023. The following search strings and Medical Subject Headings (MeSH terms) were used: "Diabetes Mellitus," "Leptin," "NPY," and "Biomarker." This article aims to discuss the physiology of leptin in type 2 DM, its glucoregulatory actions, its relationship with appetite, the impact that various lifestyle modifications can have on leptin levels, and, finally, explore leptin as a potential target for various treatment strategies.

The clinical use of insulin to treat diabetes started just over 100 years ago. The past century has witnessed remarkable innovations in insulin therapy, evolving from animal organ extracts to bioengineered human insulins with ultra-rapid onset or prolonged action. Insulin delivery systems have also progressed to current automated insulin delivery systems. In this review, we discuss the history of insulin and the pharmacology and therapeutic indications for a variety of available insulins, especially newer analog insulins. We highlight recent advances in insulin pump therapy and review evidence on the therapeutic benefits of automated insulin delivery. As with any form of progress, there have been setbacks, and insulin has recently faced an affordability crisis. We address the challenges of insulin accessibility, along with recent progress to improve insulin affordability. Finally, we mention research on glucose-responsive insulins and hepato-preferential insulins that are likely to shape the future of insulin therapy.

An estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of islets from gene-edited pigs, if successful, would resolve this problem. Pigs are now available in which the expression of the three known xenoantigens against which humans have natural (preformed) antibodies has been deleted, and in which several human 'protective' genes have been introduced. The transplantation of neonatal pig islets has some advantages over that of adult pig islets. Transplantation into the portal vein of the recipient results in loss of many islets from the instant blood-mediated inflammatory reaction (IBMIR) and so the search for an alternative site continues. The adaptive immune response can be largely suppressed by an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway, whereas conventional therapy (e.g., based on tacrolimus) is less successful. We suggest that, despite the need for effective immunosuppressive therapy, the transplantation of 'free' islets will prove more successful than that of encapsulated islets. There are data to suggest that, in the absence of rejection, the function of pig islets, though less efficient than human islets, will be sufficient to maintain normoglycemia in diabetic recipients. Pig islets transplanted into immunosuppressed nonhuman primates have maintained normoglycemia for periods extending more than two years, illustrating the potential of this novel form of therapy.

Sympathetic innervation plays a crucial role in maintaining energy balance and contributes to metabolic pathophysiology. Recent evidence has begun to uncover the innervation landscape of sympathetic projections and sheds light on their important functions in metabolic activities. Additionally, the immune system has long been studied for its essential roles in metabolic health and diseases. In this review, the aim is to provide an overview of the current research progress on the sympathetic regulation of key metabolic organs, including the pancreas, liver, intestine, and adipose tissues. In particular, efforts are made to highlight the critical roles of the peripheral nervous system and its potential interplay with immune components. Overall, it is hoped to underscore the importance of studying metabolic organs from a comprehensive and interconnected perspective, which will provide valuable insights into the complex mechanisms underlying metabolic regulation and may lead to novel therapeutic strategies for metabolic diseases.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells by the immune system. Although conventional therapeutic modalities, such as insulin injection, remain a mainstay, recent years have witnessed the emergence of novel treatment approaches encompassing immunomodulatory therapies, such as stem cell and β-cell transplantation, along with revolutionary gene-editing techniques. Notably, recent research endeavors have enabled the reshaping of the T-cell repertoire, leading to the prevention of T1D development. Furthermore, CRISPR-Cas9 technology has demonstrated remarkable potential in targeting endogenous gene activation, ushering in a promising avenue for the precise guidance of mesenchymal stem cells (MSCs) toward differentiation into insulin-producing cells. This innovative approach holds substantial promise for the treatment of T1D. In this review, we focus on studies that have developed T1D models and treatments using gene-editing systems.

Diabetes mellitus affects carbohydrate homeostasis but also influences fat and protein metabolism. Due to ophthalmic complications, it is a leading cause of blindness worldwide. The molecular pathology reveals that nuclear factor kappa B (NFκB) has a central role in the progression of diabetic retinopathy, sharing this signaling pathway with another major retinal disorder, glaucoma. Therefore, new therapeutic approaches can be elaborated to decelerate the ever-emerging "epidemics" of diabetic retinopathy and glaucoma targeting this critical node. In our review, we emphasize the role of an improvement of lifestyle in its prevention as well as the use of phytomedicals associated with evidence-based protocols. A balanced personalized therapy requires an integrative approach to be more successful for prevention and early treatment.

Mankind continues to suffer from the ever-growing diabetes epidemic and the rapid rise of type 2 diabetes mellitus (T2DM). This metabolic disease has been studied since ancient civilizations. The Arabo-Islamic civilization excelled in establishing some of the most notable discoveries and teachings that remained the blueprint for years to come in the field of diabetology.

This article aimed to review the ancient history of diabetes mellitus, with its main focus on the Arabo-Islamic civilization, and to report our subjective views and analysis of some of the past recommendations based on modern-day findings. Discussion. It is natural to have the teachings of medicine dynamically inspired by one civilization to another, as various fields continue to expand and evolve. This also applies to diabetology as the Arabo-Islamic world used the outlines of prior civilizations to revolutionize the understanding of the disease. Al-Razi and Ibn Sina are probably two of the most renowned polymaths in history, and their contributions to diabetology are well documented. Ibn Maymun's postulation about the higher prevalence of diabetes in Egypt as compared to Andalusia is something to be carefully studied. It could be that diabetes mellitus' underdiagnosis and late-stage detection are some of the major reasons for the disparity between the two mentioned regions. Modern-day Arabo-Islamic scholars continue to excel in revolutionizing diabetology.

The Arabo-Islamic world houses an impressive bout of scholars who have contributed since the ancient times to diabetology. This scientific locomotion shows no signs of stopping, as it continues to shine during the present day, and likely in the future.

There is a recent increase in the worldwide prevalence of both obesity and diabetes. In this review we assessed insulin signaling, genetics, environment, lipid metabolism dysfunction and mitochondria as the major determinants in diabetes and to identify the potential mechanism of gut microbiota in diabetes diseases. We searched relevant articles, which have key information from laboratory experiments, epidemiological evidence, clinical trials, experimental models, meta-analysis and review articles, in PubMed, MEDLINE, EMBASE, Google scholars and Cochrane Controlled Trial Database. We selected 144 full-length articles that met our inclusion and exclusion criteria for complete assessment. We have briefly discussed these associations, challenges, and the need for further research to manage and treat diabetes more efficiently. Diabetes involves the complex network of physiological dysfunction that can be attributed to insulin signaling, genetics, environment, obesity, mitochondria and stress. In recent years, there are intriguing findings regarding gut microbiome as the important regulator of diabetes. Valid approaches are necessary for speeding medical advances but we should find a solution sooner given the burden of the metabolic disorder - What we need is a collaborative venture that may involve laboratories both in academia and industries for the scientific progress and its application for the diabetes control.

Single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 4 (TLR4) gene have been documented in type 2 diabetes mellitus (T2DM) and other diseases in the Saudi population. We investigated the relationship between rs11536889, rs4986790, and rs4986791 SNPs in the TLR4 gene and T2DM in the Saudi population; 105 patients with T2DM and 105 healthy controls were analyzed. The TLR4 gene was amplified through PCR, followed by restriction fragment length polymorphism analysis for rs4986791 and Sanger sequencing for rs11536889 and rs4986790 SNPs. The clinical and biochemical characteristics were associated with T2DM (p < 0.05). The rs11536889, rs4986790, and rs4986791 SNPs in control subjects followed the Hardy-Weinberg equilibrium (p > 0.05). Alleles were associated with rs11536889, rs4986791, heterozygous codominant, and dominant models (p < 0.05). However, the rs4986790 SNP was not associated with T2DM (p > 0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol (HDLc) levels were associated with T2DM (p < 0.001). Analysis of variance showed that waist (p = 0.0005) and hip circumferences (p = 0.002) in rs4986790 and rs4986791 SNPs, in SBP (p = 0.001), DBP (p = 0.002), and HDLc levels (p = 0.003), were associated with T2DM subjects. T2DM was also associated with the haplotype (p < 0.001) but not with linkage disequilibrium. The gene-gene interaction was associated with the three SNPs studied in patients with T2DM according to the generalized multifactor dimensionality reduction model (p < 0.0001). Dendrogram and graphical depletion analysis revealed a moderate association in patients with T2DM. The results suggest that rs11536889 and rs4986790 SNPs are genotypically and allelically associated with T2DM in Saudi patients. Future functional studies are recommended to validate the genetic roles of these SNPs in the pathogenesis and progression of diseases.

Body-based biomolecular sensing systems, including wearable, implantable and consumable sensors allow comprehensive health-related monitoring. Glucose sensors have long dominated wearable bioanalysis applications owing to their robust continuous detection of glucose, which has not yet been achieved for other biomarkers. However, access to diverse biological fluids and the development of reagentless sensing approaches may enable the design of body-based sensing systems for various analytes. Importantly, enhancing the selectivity and sensitivity of biomolecular sensors is essential for biomarker detection in complex physiological conditions. In this Review, we discuss approaches for the signal amplification of biomolecular sensors, including techniques to overcome Debye and mass transport limitations, and selectivity improvement, such as the integration of artificial affinity recognition elements. We highlight reagentless sensing approaches that can enable sequential real-time measurements, for example, the implementation of thin-film transistors in wearable devices. In addition to sensor construction, careful consideration of physical, psychological and security concerns related to body-based sensor integration is required to ensure that the transition from the laboratory to the human body is as seamless as possible.

Whole-organ pancreas and islets transplantations are two therapeutic options to treat type 1 diabetic patients resistant to optimised medical treatment in whom severe complications develop. Selection of the best option for β-cell replacement depends on several factors such as kidney function, patient comorbidities, and treatment goals. For a patient with end-stage kidney disease, the treatment of choice is often a simultaneous transplant of the pancreas and kidney (SPK). However, it remains a major surgical procedure in patients with multiple comorbidities and therefore it is important to select those who will benefit from it. Additionally, in view of the organ shortage, new strategies to improve outcomes and reduce immune reactions have been developed, including dynamic organ perfusion technologies, pancreas bioengineering, and stem cell therapies. The purpose of this article is to review the indications, surgical techniques, outcomes, and future directions of whole-organ pancreas and islets transplantations.

Diabetes is the ninth leading cause of death, directly accounting for 1.5 million deaths annually worldwide. Despite several breakthrough discoveries, little progress has been made in type 2 diabetes outcomes over the past 100 years. Younger age (below 60 years), a diet high in calories and processed food, and severe obesity (body mass index >35 kg/m²) may identify reversible beta cell dysfunction. Much of the clinical presentation pertains to flooding the body's adaptive limits with overnutrition. Recognizing this as a global societal trend brought about by lifestyle changes, sedentary work, mental stress and unlimited access to calorie-dense foods is crucial. Insulin resistance and genetic abnormalities cannot account for the dramatic increase in diabetes, from only 1% five decades ago to nearly 10% today. Obesity - and not insulin resistance - is at the core of the problem. As well as hyperglycaemia, end-organ damage can also be reversed with diet and weight loss in many affected individuals. We present the evolution of our understanding and compelling reasons to reframe diabetes in the severely obese to what it really is - overweight hyperglycaemia. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles. The objective of this review is to better understand global trends and the potential to improve outcomes by reframing the diabetes narrative towards remission. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles.

Diabetic neuropathy is the most common microvascular complication of diabetes mellitus and a major risk factor for diabetes-related lower-extremity complications. Diffuse neuropathy is the most frequently encountered pattern of neurological dysfunction and presents clinically as distal symmetrical sensorimotor polyneuropathy. Due to the increasing public health significance of diabetes mellitus and its complications, screening for diabetic peripheral neuropathy is essential. Consequently, a review of the principles that guide screening practices, especially in resource-limited clinical settings, is urgently needed.

Numerous evidence-based assessments are used to detect diabetic peripheral neuropathy. In accordance with current guideline recommendations from the American Diabetes Association, International Diabetes Federation, International Working Group on the Diabetic Foot, and National Institute for Health and Care Excellence, a screening algorithm for diabetic peripheral neuropathy based on multiphasic clinical assessment, stratification according to risk of developing diabetic foot syndrome, individualized treatment, and scheduled follow-up is suggested for use in resource-limited settings.

Screening for diabetic peripheral neuropathy in resource-limited settings requires a practical and comprehensive approach in order to promptly identify affected individuals. The principles of screening for diabetic peripheral neuropathy are: multiphasic approach, risk stratification, individualized treatment, and scheduled follow-up. Regular screening for diabetes-related foot disease using simple clinical assessments may improve patient outcomes.

Diabetes mellitus is a growing disease that affects people of different ages due to deficiencies in insulin action and secretion. Diabetes causing long-term hyperglycemia damages, destroys, and fails essential organs, including kidneys, eyes, hearts, nerves, and blood vessels. The involvement of pathogenic factors makes diabetes mellitus a severe disease. The autoimmune process results in insulin deficiency by destroying the beta-cells in the pancreas. This leads to insulin resistance. As a result of defects and abnormalities in fat, carbohydrate, and protein synthesis, insulin does not work as it should on the target tissues. As diabetes mellitus becomes, more severe, long-term and effective treatment becomes necessary. A wide range of nanomaterials can be used to treat diabetes mellitus in patients. In addition to being potential imaging, diagnostic, and treatment agents for diabetes mellitus, carbon nanomaterials (CNMs) are another group of nanoparticles that exhibit potential interest. The CNMs acts as implantable nanosensor to track and detect blood glucose level in patients with diabetes. CNMS are possible drug carriers that can treat diabetes mellitus selectively, precisely, and effectively. Diabetes mellitus can be diagnosed and treated with CNMs due to their structural specificity and high drug-loading efficiency. The present review explores CNMs for their types, synthesis, and anti-diabetic properties. This review aims to provide a detailed view of the new technology that can be used to decipher the mechanism of CNMs in diabetes mellitus.

Efficient signal transduction is important in maintaining the function of the nervous system across tissues. An intact neurotransmission process can regulate energy balance through proper communication between neurons and peripheral organs. This ensures that the right neural circuits are activated in the brain to modulate cellular energy homeostasis and systemic metabolic function. Alterations in neurotransmitters secretion can lead to imbalances in appetite, glucose metabolism, sleep, and thermogenesis. Dysregulation in dietary intake is also associated with disruption in neurotransmission and can trigger the onset of type 2 diabetes (T2D) and obesity. In this review, we highlight the various roles of neurotransmitters in regulating energy balance at the systemic level and in the central nervous system. We also address the link between neurotransmission imbalance and the development of T2D as well as perspectives across the fields of neuroscience and metabolism research.

Insulin pump therapy is a real breakthrough in managing diabetes Mellitus, particularly in children. It can deliver a tiny amount of insulin and decreases the need for frequent needle injections. It also helps to maintain adequate and optimal glycemic control to reduce the risk of metabolic derangements in different tissues. Children are suitable candidates for pump therapy as they need a more freestyle and proper metabolic control to ensure adequate growth and development. Therefore, children and their caregivers should have proper education and training and understand the proper use of insulin pumps to achieve successful pump therapy. The pump therapy continuously improves to enhance its performance and increase its simulation of the human pancreas. Nonetheless, there is yet a long way to reach the desired goal.

To review discusses the history of pump development, its indications, types, proper use, special conditions that may enface the children and their families while using the pump, its general care, and its advantages and disadvantages.

We conducted comprehensive literature searches of electronic databases until June 30, 2022, related to pump therapy in children and published in the English language.

We included 118 articles concerned with insulin pumps, 61 were reviews, systemic reviews, and meta-analyses, 47 were primary research studies with strong design, and ten were guidelines.

The insulin pump provides fewer needles and can provide very tiny insulin doses, a convenient and more flexible way to modify the needed insulin physiologically, like the human pancreas, and can offer adequate and optimal glycemic control to reduce the risk of metabolic derangements in different tissues.

Diabetes is an increasingly common chronic metabolic disorder in children worldwide. The discovery of insulin in 1921 resulted in unprecedented advancements that improved the lives of children and youth with diabetes. The purpose of this article is to review the history of diabetes in children and youth over the last century and its implications for future developments in the field. We identified 68 relevant events between 1921 and 2021 through literature review and survey of pediatric endocrinologists. Basic research milestones led to the discovery of insulin and other regulatory hormones, established the normal physiology of carbohydrate metabolism and pathophysiology of diabetes, and provided insight into strategies for diabetes prevention. While landmark clinical studies were initially focused on adult diabetes populations, later studies assessed etiologic factors in birth cohort studies, evaluated technology use among children with diabetes, and investigated pharmacologic management of youth type 2 diabetes. Technological innovations culminated in the introduction of continuous glucose monitoring that enabled semi-automated insulin delivery systems. Finally, professional organizations collaborated with patient groups to advocate for the needs of children with diabetes and their families. Together, these advances transformed type 1 diabetes from a terminal illness to a manageable disease with near-normal life expectancy and increased our knowledge of type 2 diabetes and other forms of diabetes in the pediatric population. However, disparities in access to insulin, diabetes technology, education, and care support remain and disproportionately impact minority youth and communities with less resources. The overarching goal of diabetes management remains promoting a high quality of life and improving glycemic management without undermining the psychological health of children and youth living with diabetes.

Nearly 100 years ago, diabetes, a disease expected to reach global prevalence of at least 10% within the decade, was a fatal diagnosis. This year of 2022 marks a century since insulin, a lifesaving treatment for those living with diabetes, was purified, tested in humans, and brought to the bedside through widespread commercial production, thus saving countless lives. Insulin's arrival to the world stage was acknowledged with the 1923 Nobel Prize in Physiology or Medicine for "the discovery of insulin", the first among several Prizes awarded to honor scientific work on insulin. This initial awarding has been the subject of significant controversy since, as numerous other scientists paved the way towards the ultimate success, and priority for the true "discovery of insulin" has been argued for many other scientists. The intention and regulations around the Nobel Prize nomination and award process presented herein offer insight into the 1923 Nobel prize designation for the Toronto group, which distinguished itself in the accomplishment by their success in purifying insulin from pancreatic extract and in bringing insulin to worldwide production and the homes of those who needed it. However, a continuous, collaborative process involving contributors spanning centuries and continents was required for the development, rather than discovery, of insulin therapy and its benefits to humanity. This should be the story's enduring legacy. The prior 100 years have witnessed a series of significant innovations in insulin development and therapeutics, but both a cure for diabetes and equitable insulin access remain out of reach and require inspired attention and continuous diligent efforts.

The first preparation of insulin extracted from a pancreas and made suitable for use in humans after purification was achieved 100 years ago in Toronto, an epoch-making achievement, which has ultimately provided a life-giving treatment for millions of people worldwide. The earliest animal-derived formulations were short-acting and contained many impurities that caused adverse reactions, thereby limiting their therapeutic potential. However, since then, insulin production and purification improved with enhanced technologies, along with a full understanding of the insulin molecule structure. The availability of radio-immunoassays contributed to the unravelling of the physiology of glucose homeostasis, ultimately leading to the adoption of rational models of insulin replacement. The introduction of recombinant DNA technologies has since resulted in the era of both rapid- and long-acting human insulin analogues administered via the subcutaneous route which better mimic the physiology of insulin secretion, leading to the modern basal-bolus regimen. These advances, in combination with improved education and technologies for glucose monitoring, enable people with diabetes to better meet individual glycaemic goals with a lower risk of hypoglycaemia. While the prevalence of diabetes continues to rise globally, it is important to recognise the scientific endeavour that has led to insulin remaining the cornerstone of diabetes management, on the centenary of its first successful use in humans.

A significantly high percentage of hospitalized COVID-19 patients with diabetes mellitus (DM) had severe conditions and were admitted to ICU. In this review, we have delineated the plausible molecular mechanisms that could explain why there are increased clinical complications in patients with DM that become critically ill when infected with SARS-CoV2. RNA viruses have been classically implicated in manifestation of new onset diabetes. SARS-CoV2 infection through cytokine storm leads to elevated levels of pro-inflammatory cytokines creating an imbalance in the functioning of T helper cells affecting multiple organs. Inflammation and Th1/Th2 cell imbalance along with Th17 have been associated with DM, which can exacerbate SARS-CoV2 infection severity. ACE-2-Ang-(1-7)-Mas axis positively modulates β-cell and cardiac tissue function and survival. However, ACE-2 receptors dock SARS-CoV2, which internalize and deplete ACE-2 and activate Renin-angiotensin system (RAS) pathway. This induces inflammation promoting insulin resistance that has positive effect on RAS pathway, causes β-cell dysfunction, promotes inflammation and increases the risk of cardiovascular complications. Further, hyperglycemic state could upregulate ACE-2 receptors for viral infection thereby increasing the severity of the diabetic condition. SARS-CoV2 infection in diabetic patients with heart conditions are linked to worse outcomes. SARS-CoV2 can directly affect cardiac tissue or inflammatory response during diabetic condition and worsen the underlying heart conditions.

The year 2021 marked the centenary of the isolation of a therapeutic form of insulin and its successful use in dogs. This was a landmark moment that subsequently and rapidly led to the commercial manufacture of insulin for use in humans. The impact of insulin was almost miraculous as those destined to die from their diabetes mellitus returned to life. Over the past 100 years, insulin formulations have been modified to attempt to provide a predictable and prolonged duration of action while avoiding the development of hypoglycaemia. This has led to an ever-growing variety of insulin types in human medicine, many of which have subsequently been used in dogs. The purpose of this review article is to provide an overview of available insulin types and their application to the chronic management of canine diabetes mellitus.